Effects of IMAGENT on pulmonary hemodynamics and gas exchange in dogs

Imagent is an IV injected contrast echocardiography agent designed to image the left ventricle after traversing the pulmonary circulation. We examined the effect of Imagent on pulmonary function by injecting either Imagent (n = 8) or equivalent volume of saline (n = 7) IV in randomly ordered 1, 8 and 16 mg/kg doses in dogs with preexisting pulmonary hypertension. We found that Imagent had no effects on cardiac output, pulmonary gas exchange, lung wet:dry ratio or static compliance. However, the 16 mg/kg dose of Imagent increased both pulmonary artery pressure (PAP) transiently by an average of 5.7 mmHg (p < 0.05) 2 to 3 min after injection and pulmonary vascular resistance (PVR) by 5.9 mmHg per l/min (p < 0.05) 4 min after injection before returning to preinjection levels. The lower doses of Imagent did not affect PAP or PVR. These results imply that the approved clinical dose of Imagent (0.125 mg/kg) will not affect pulmonary hemodynamics, gas exchange or mechanical properties in dogs with preexisting pulmonary hypertension.     

Effects of elastic loading and exercise on pulmonary gas exchange in dogs.

We assessed the effects of negative intrathoracic pressure induced by inspiratory elastic loading on pulmonary, gas exchange with and without electrically induced hindlimb exercise in 8 normal, anesthetized dogs. Two elastic loads (EL) were used; one of 81 and one of 140 cmH2O/liter. These are equivalent to doubling and tripling the normal elastance of the dog's respiratory system, respectively. Elastic loading decreased ventilation and caused hypoxemia and hypercapnia, but it did not affect systemic arterial pressure or heart rate. During exercise, increase in ventilation was limited, whereas increase in cardiac output was not affected by elastic loading. Alveolar-arterial O2 tension difference (A-aDO2) was not changed significantly by exercise alone. However, elastic loading accompanied by exercise increased A-aDO2. Although comparable end-inspiratory pleural pressure was achieved with large EL (-29 +/- 2 cmH2O, mean +/- SE) and small EL with exercise (-30 +/- 2 cmH2O), the latter increased A-aDO2 whereas the former did not. Large negative intrapleural pressure combined with increased cardiac output may have caused transient interstitial edema.     

Intravenous administration of choline or cdp-choline improves platelet count and platelet closure times in endotoxin-treated dogs

This study was performed to assess the effects of intravenous choline chloride and cytidine-5'-diphosphate choline (CDP-choline) treatments on circulating platelet, white blood cell, and red blood cell counts and platelet functions in response to endotoxin. Saline (0.2 mL/kg), choline chloride (20 mg/kg), or CDP-choline (70 mg/kg) were given intravenously three times at 4-h intervals, and endotoxemia was induced by endotoxin (E. coli 055:B5, 20 microg/kg) infusion, 5 min after the first treatment. Blood samples were collected before and at multiple time points after the challenge, for a panel of hematologic parameters and platelet closure times measured by PFA-100. In saline-treated dogs, circulating platelet counts decreased by 85% (P < 0.001) at 0.5 h and remained low by 36%-80% (P < 0.5-0.001) 1-12 h after endotoxin. Circulating WBC counts decreased by 80%-90% (P < 0.001) at 0.5-2 h, and increased (P < 0.001) by 190% 12 h after the endotoxin. In response to endotoxin, RBCs increased by 10%-13% (P < 0.05) at 1-12 h. Endotoxin-induced decline in circulating platelets was attenuated at 0.5 h (P < 0.05-0.01) and reversed at 1-12 h (P < 0.05-0.001) by choline. Platelet closure times were shortened from 81 +/- 10 s and 135 +/- 10 s to 29 +/- 5 s (P < 0.001) and 60 +/- 3 s (P < 0.001) at 0.5 h, and prolonged (P < 0.001) at 1-8 h after endotoxin induction. Endotoxin-induced shortening in platelet closure times was attenuated (P < 0.05) and blocked (P < 0.01) by choline and CDP-choline, respectively. These results showed that choline and CDP-choline treatments improved circulating platelet counts and platelet function during endotoxemia in dogs.     

Perfluorocarbon-associated gas exchange

BACKGROUND AND METHODS: Liquid ventilation with oxygenated perfluorocarbon eliminates surface tension due to pulmonary air/fluid interfaces, and improves pulmonary function and gas exchange in surfactant deficiency. In liquid ventilation, perfluorocarbon is oxygenated, purged of CO2, and cycled into and out of the lungs using an investigational device. A new approach, perfluorocarbon-associated gas exchange, uses a conventional ventilator and combines features of liquid ventilation and continuous positive-pressure breathing. In 13 normal piglets, a volume of perfluorocarbon equivalent to the normal functional residual capacity (30 mL/kg) was instilled into the trachea, left in situ, and volume-regulated gas ventilation (FIO2 1.0) was resumed. For 1 hr, perfluorocarbon was continuously bubble-oxygenated within the lungs, where it directly participated in gas exchange. RESULTS: PaO2 and PaCO2 averaged 401 +/- 51 and 40 +/- 4 torr (53.6 +/- 6.8 and 5.3 +/- 0.5 kPa), respectively. Peak airway pressure during perfluorocarbon-associated gas exchange (22 +/- 2 cm H2O at 1 hr) and during continuous, positive-pressure breathing (23 +/- 4 cm H2O) were nearly identical. Venous oxygen saturation and pH were normal (73 +/- 8% and 7.43 +/- 0.05, respectively, at 1 hr). CONCLUSIONS: Perfluorocarbon-associated gas exchange was uniformly well tolerated, and its efficiency approached that of continuous positive-pressure breathing. Applications of perfluorocarbon technology to lung disease may not be limited by existing instrumentation.     

External cardiopulmonary resuscitation preserves brain viability after prolonged cardiac arrest in dogs.

Standard external cardiopulmonary resuscitation (CPR) steps A-B-C produce a low blood flow that may or may not preserve brain viability during prolonged cardiac arrest. A dog model was used with ventricular fibrillation (VF) of 20 minutes, reperfusion with brief cardiopulmonary bypass, controlled ventilation to 20 hours, and intensive care to 96 hours. A retrospective comparison was made of the results of one series, now called "group I" (n = 10)--which received CPR basic life support interposed from VF 10 to 15 minutes, and CPR advanced life support with epinephrine (without defibrillation) from VF 15 to 20 minutes--to the results of another series, now "control group II" (n = 10)--which received VF no flow (no CPR) for 20 minutes. All 20 dogs within protocol were resuscitated. All 10 of group I and 7 of 10 of group II survived to 96 hours. Pupillary light reflex returned after the start of cardiopulmonary bypass at 7.7 +/- 3.7 minutes in CPR group I, versus 16.3 +/- 7.4 minutes in control group II (P = .032). At 96 hours postarrest, final overall performance categories (1, normal; 5, brain death) were better in group I. Six of 10 dogs achieved normality (overall performance category 1) in group I, as compared with none of 10 in group II (P = .004). Final neurologic deficit score (0%, best; 100% worst) was lower (better) in group I (15% +/- 20%) than in group II (51% +/- 6%; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Alteration in gas exchange related to body position

The diagnosis of alteration in gas exchange related to body position requires a deliberate evaluation of PaO2 responses. Body positions that improve V/Q matching and thus PaO2 need to be specified in patient care plans; individualized interventions are more useful than generic care plans that state, "turn q 2 h." Additionally, standard rotations for patients treated on mechanically rotating beds could be individualized according to gas exchange responses to the position changes. Routine documentation of patient body positions next to arterial blood gas results on flow sheets could prove valuable in the evaluation and treatment of hypoxemia in patients with pulmonary problems.     

Artifacts in the assessment of metabolic gas exchange

In mechanically ventilated patients metabolic gas exchange recordings are frequently influenced by routine patient therapy. In this study the influence of such artifacts is investigated and a method for automatic detection and suppression proposed. This method reduced the influence of artifacts on diurnal oxygen and carbon dioxide exchange from up to 10% to a maximum of 1%.     

Transcutaneous measurement of gas exchange parameters in anesthesiologic practice

pO2 and pCO2 were studied transcutaneously (tcpO2 and tcpCO2) in 36 patients during reconstructive surgery performed under various multicomponent balanced anesthesia techniques. The results, in the absence of hemodynamic disturbances, serve as a reliable indication of changes in arterial blood pO2 and pCO2 (PaO2 and PaCO2), however, it is impossible to identify transcutaneous PaO2 and PaCO2 values. A decrease in tcpO2 and an increase in tcpCO2 during their dynamic study may give evidence of the inadequacy of controlled lung ventilation. At the same time, with normal PaO2 and PaCO2 values, hypoxia and hypercarbia, recorded, using transcutaneous transducers, may serve as an early index of central and peripheral hemodynamic disturbances. It is advisable to use the results of transcutaneous pO2 and pCO2 measurements as additional tests, characterizing O2 and CO2 transport.     

Non-steady state monitoring by respiratory gas exchange

Traditionally, the study of CO₂ and O₂ kinetics in the body has been mostly confined to equilibrium conditions. However, the peri-anesthesia period and the critical care arena often involve conditions of non-steady state. The detection and explanation of CO₂ kinetics during non-steady state pathophysiology have required the development of new methodologies, including the CO₂ expirogram, average alveolar expired PCO₂, and CO₂ volume exhaled per breath. Several clinically relevant examples of non-steady state CO₂ kinetics perturbations are examined, including abrupt decrease in cardiac output, application of positive end-expiratory pressure during mechanical ventilation, and occurrence of pulmonary embolism. The lesser known area of non-steady state O₂ kinetics is introduced, including the measurement of pulmonary O₂ uptake per breath. Future directions include the study of the respiratory quotient per breath, where the anaerobic threshold during anesthesia is identified by increasing respiratory quotient. This revised version was published online in July 2006 with corrections to the Cover Date.     

Models for estimating the change-point in gas exchange data

In subjects undertaking an incremental exercise test to exhaustion, the onset of metabolic acidosis can be detected by an increased rate of carbon dioxide output (VCO2) relative to the rate of increase of oxygen uptake (VO2). To locate the change-point (the gas exchange threshold) in such subjects, a two-line regression model relating these two quantities has been used, where the location of the change-point is unknown. We argue that statistical models where the change-point is set on time (rather than VO2) are more appropriate. This is because VO2 is not monotone in time. We use novel statistical methodology of hidden Markov models to demonstrate the existence of the change-point. We use time series models, to estimate the position of the change-point. In these models distributions other than the multivariate normal are considered. For some subjects, the variance of VCO2 increases with time because of increasing ventilation and this is also modelled. The results are illustrated using gas exchange data on three healthy subjects who performed a 20 W min(-1) workrate ramp test.     

Intralipid alterations in pulmonary prostaglandin metabolism and gas exchange

To assess the role of Intralipid as a prostaglandin (PG) precursor, we infused Intralipid into 40 rabbits with long-term arterial and venous catheters; 24 other rabbits received a control saline infusion. One-half of the rabbits in both experimental and control groups had oleic acid-damaged lungs, and at least 5 in each of the 4 groups (Intralipid/saline in normal/damaged lungs) received indomethacin. Two vasodilating PGs (E2 and 6KF1 alpha) and one vasoconstricting PG (F2 alpha) were measured. Triglyceride levels increased significantly in all Intralipid groups, averaging 580 mg/dl. Intralipid-related alterations in PG levels and arterial oxygen tension (PaO2) were significant only in the lung-damaged group. The mean (+/- sem) decrease in PaO2 was 12 +/- 1.5 torr (p less than .001). For both vasodilating PGs, Intralipid infusion increased the pulmonary arteriovenous gradients for PG E2 and PG 6KF1 alpha by 960 pg/ml (p less than .05) and 697 pg/ml (p less than .10), respectively. Both the PaO2 decrease and the vasodilating PG increases were blocked by indomethacin. In summary, Intralipid infusion in lung-damaged rabbits increased pulmonary production of vasodilating PGs and associated hypoxemia, presumably caused by an unblocking of hypoxic vasoconstriction and resultant increase in intrapulmonary right-to-left shunt.